Diflunisal, a fluorinated salicylate, exhibits analgesic, anti-inflammatory and antipyretic properties, and at high doses inhibits prostaglandin synthesis. It is well absorbed from the intestines and reaches peak plasma levels within 2-3 hours; steady state plasma levels are reached within 3-9 days on a regimen off 500 mg twice daily. Plasma Diflunisal is 99.83% protein bound and it is excreted mostly in the urine as a glucuronide. Diflunisal is generally better tolerated than aspirin and the most frequent adverse reactions are nausea, gastrointestinal discomfort and diarrhea.
The inhibitory action of diflunisal on cyclooxygenase metabolism has been represented by: Verbeeck, R. K. et al., Clin. Pharmac., 8:297 (1983); Steelman, S. L. et al., i Clin. Ther. 1(Suppl):1 (1978); Tempero, K. F. et al., Br. J. Clin. Pharmacol., 4(Suppl):31S (1977); and by Davis, R. O., Pharmacotherapy, 3:9S (1983). However, no ocular effects have been reported. Diflunisal has exceptionally high binding to plasma albumin, 99.83% at a concentration of 50 .mu.m/ml, and thus can unbind partially bound compounds such as salicylic acid and phenprocoumin (Verbeeck, R. K., et al, Biochem. Pharmacal. 29:571 (1980)).
Examples of heterocyclic sulfonamides and phenylbenzoic acid compounds useful in the practice of this invention are given in U.S. Pat. Nos. 3,714,226 (Ruyle et al); 2,980,679 (Pala et al); 2,554,816; 4,636,515 and 4,483,864 (Barfknecht et al); 3,991,206 (Tolman et al); 4,305,927 (Theeuwes et al); 4,438,123 (Smith); and in 4,619,939 (Maren); all of which are included herein by reference. Topical application of sulfonamides for the reduction of intraocular pressure is shown in U.S. 4,619,939; U.S. 483,864; U.S. 4,438,123 and in U.S. 4,636,515. Sulfonamides and their preparation are shown in U.S. 2,980,679 and U.S. 554,816. The oral administration of acetazolamide for controlling intraocular pressure is shown in U.S. 4,305,927. In U.S. 3,714,226 various 5-(phenyl) benzoic acid compounds are shown to be useful anti-inflammatory compounds. Topical application of p-biphenylacetic acid as an ocular inflammatory agent is shown in U.S. 3,991,206.